Definitions

Subpart B: Subpart B is found in 45 CFR 46 (DHHS) and includes additional protections for neonates involved in research (45 CFR 46.205).

Neonate: Newborns from the time of delivery up until 28 days old.

Nonviable neonate: A neonate after delivery that, although living, is not viable.

Viable: As it pertains to the neonate, means being able, after delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heartbeat and respiration.

Guidance

Federal regulations require additional safeguards when approving research involving neonates. These special protections are found in Subpart B of 45 CFR 46. The IRB may approve research involving neonates only if the research meets the criteria outlined in Subpart B, provided that the research also meets the general criteria for approval.

The IRB must consider the general criteria for IRB approval for all studies, including those that involve neonates. In determining whether the general criteria for approval are met, the IRB may have additional considerations for the research that would generally not be of concern in an adult population. Risks that may be considered minimal when dealing with adults (e.g., blood draw) may be riskier when applied to a neonate population. Efforts should be made to minimize any potential harm.

Additional Protections for the Inclusion of Neonates in Research

The IRB must consider the degree of risk and discomfort involved in the research in relation to the direct benefits it offers to the neonate to determine whether the study is approvable under the federal regulations. The standard of review is conducted consistently, regardless of full board or expedited review. The IRB may approve studies involving neonates only if the research meets the following criteria, according to the viability of the neonate:

Research Involving Viable Neonates

A newborn (neonate 0-28 days) who is considered viable may be included in the research under federal regulations for children. The regulations governing research involving children are outlined in both 45 CFR 46 (DHHS) and 21 CFR 50 (FDA) as Subpart D. Requirements for including children in research are described in the Guidance Topic: Children.

Research Involving Neonates of Uncertain Viability

If the viability of the neonate will not be determined during  the study, the IRB may approve the study involving neonates only if the research fits into either category 1 or 2 below and also meets all 3 of the following considerations:

Category 1: The research holds out the prospect of enhancing the probability of survival of the neonate to the point of viability. Any risk to the neonate is the least possible for achieving the objective of enhancing the probability of survival of the neonate to the point of viability.

Category 2: The purpose of the research is the development of important biomedical knowledge which cannot be obtained by other means and there will be no added risk to the neonate resulting from the research.

Additional Considerations (1-3):

1. Where scientifically appropriate, preclinical and clinical studies have been conducted and provide data for assessing potential risks to neonates;
2. Each individual providing consent is fully informed regarding the reasonable foreseeable impact of the research on the neonate;
3. Individuals engaged in the research will have no part in determining the viability of a neonate.

Research Involving Nonviable Neonates

After delivery, nonviable neonates may be included in research if the following conditions are met:

1. Where scientifically appropriate, preclinical and clinical studies have been conducted and provide data for assessing potential risks to neonates;
2. Each individual providing consent is fully informed regarding the reasonable foreseeable impact of the research on the neonate;
3. Individuals engaged in the research will have no part in determining the viability of a neonate;
4. Vital functions of the neonate will not be artificially maintained;
5. The research will not terminate the heartbeat or respiration of the neonate;
6. There will be no added risk to the neonate resulting from the research;
7. The purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means.

Because the IRB must confirm that all considerations and conditions are met for the inclusion of neonates in research, the application must have the information detailed above, as applicable. Investigators should verify that applications include all the specific information for the board to consider. See the Points to Consider section below for information and answers to questions that must be provided.

Obtaining Consent for Research Involving Neonates

Informed consent must be obtained from the necessary individuals as described below.

Research Involving Viable Neonates

Permission from a parent or guardian is required. Requirements for parental permission are described in the IRB guidance, Parental Permission and Assent.

Research Involving Neonates of Uncertain Viability

Consent from either parent of the neonate is required. If consent cannot be obtained from either parent because of unavailability, incompetence, or temporary incapacity, a legally authorized representative for the parent(s) may give consent. Requirements for legally authorized representatives are described in the IRB Guidance, Legally Authorized Representative (LAR) and Surrogate Consent.

Consent from the father does not need be obtained if the pregnancy resulted from rape or incest.

Research Involving Nonviable Neonates

Consent from both parents of the neonate is required. If consent cannot be obtained from one parent because of unavailability, incompetence, or temporary incapacity, consent from one parent will suffice. If neither parent can give consent, the neonate may not be included in the research.

Consent from the father need not be obtained if the pregnancy resulted from rape or incest.

Additional Considerations

VA Research: VA research involving neonates must follow the Office of Research & Development’s (ORD) requirements for research involving neonates as described in VHA Directive 1200.05(4), Paragraph 19. VA investigators may conduct research involving noninvasive monitoring of neonates if the research is determined by the IRB to be minimal risk. Prospective observational and retrospective record review studies that involve neonates or neonatal outcomes are permitted. The VA Medical Facility Director must certify that the medical facility has sufficient expertise in neonatal health to conduct the proposed research.

Documents and References

Additional Protections for the Inclusion of Neonates in Research (OHRP): 45 CFR 46, Subpart B

Investigator Guidance Series: Children

Investigator Guidance Series: Parental Permission and Child Assent

Points to Consider